Inhaled hypertonic saline for cystic fibrosis: Reviewing the potential evidence for modulation of neutrophil signalling and function

Abstract

Cystic fibrosis (CF) is a multisystem disorder with significantly shortened life expectancy. The major cause of mortality and morbidity is lung disease with increasing pulmonary exacerbations and decline in lung function predicting significantly poorer outcomes. The pathogenesis of lung disease in CF is characterised in part by decreased airway surface liquid volume and subsequent failure of normal mucociliary clearance. This leads to accumulation of viscous mucus in the CF airway, providing an ideal environment for bacterial pathogens to grow and colonise, propagating airway inflammation in CF. The use of nebulised hypertonic saline (HTS) treatments has been shown to improve mucus clearance in CF and impact positively upon exacerbations, quality of life, and lung function. Several mechanisms of HTS likely improve outcome, resulting in clinically relevant enhancement in disease parameters related to increase in mucociliary clearance. There is increasing evidence to suggest that HTS is also beneficial through its anti-inflammatory properties and its ability to reduce bacterial activity and biofilm formation. This review will first describe the use of HTS in treatment of CF focusing on its efficacy and tolerability. The emphasis will then change to the potential benefits of aerosolized HTS for the attenuation of receptor mediated neutrophil functions, including down-regulation of oxidative burst activity, adhesion molecule expression, and the suppression of neutrophil degranulation of proteolytic enzymes.

Keywords: Cystic fibrosis; Hypertonic saline; Mucociliary clearance; Neutrophils and inflammation

Core tip: The pathogenesis of lung disease in cystic fibrosis (CF) is characterised by decreased airway surface liquid volume and subsequent failure of normal mucociliary clearance. Therapies acting against airway mucus in CF include aerosolized hypertonic saline (HTS). It has been shown that HTS aids mucociliary clearance by restoring the liquid layer lining the airways. However, recent studies are beginning to broaden our view on the beneficial effects of HTS, which now extend to include anti-inflammatory properties. This review aims to discuss the therapeutic benefits of HTS and to identify the potential benefits of aerosolized HTS for attenuation of neutrophil function.